Nature Medicine Contents: August 2010 Volume 16 Number 8, pp 829 - 933

[Nature Medicine Alert]

Advertisement Less sample, more data. If you can run a Western, you can detect up to 274 cytokines with the RayBio® Human Cytokine Antibody Array 4000. • Easy to use • No special equipment required • Compatible with any sample type, including lysates • Use as little as 500 ul of sample • Results in 1 day • Also available in glass-slide format • Testing services available, too! TABLE OF CONTENTS August 2010 Volume 16, Issue 8 Editorial News Book Review News and Views Community Corner Between Bedside and Bench Research Highlights Brief Communication Articles Letter Technical Reports Recommend to your library Web feed Available online only Subscribe Follow us on Twitter Find us on Facebook Advertisement Nature Reviews Neuroscience FREE POSTER ON NEURAL REGULATION OF FOOD INTAKE AND ENERGY BALANCE Obesity has reached epidemic proportions worldwide and can diminish both the quality and length of life. The causes may lie in the circuitry of brain areas that regulate foodseeking behaviour in coordination with peripheral hormonal signalling. This poster provides an overview of some of the molecules and circuits involved in the regulation of food intake and energy balance. Download this Poster for FREE   Nature Medicine Podcast  Top Patch up   We explore new microneedle patches that may take the sting out of vaccine shots and a choral work that transforms the singers' own genetic code into music. Listen Now Editorial Top A cure for cancer research p829 doi:10.1038/nm0810-829 The National Cancer Institute is the most important cancer funding agency in the US. Yet criticism of some of its programs underscores the need for change and modernization of this institute. With the recent appointment of a new NCI director, the time for change has arrived. Full Text | PDF News Top After Avandia, some seek split in drug approval and monitoring p831 Elie Dolgin doi:10.1038/nm0810-831 Full Text | PDF Chronic controversy continues over mysterious XMRV virus p832 Elie Dolgin doi:10.1038/nm0810-832a Full Text | PDF Fewer shots proposed to increase uptake of HPV vaccine pp832 - 833 Kirsten Dorans doi:10.1038/nm0810-832b Full Text | PDF Fight for subject confidentiality threatens disaster research p833 Stu Hutson doi:10.1038/nm0810-833 Full Text | PDF Gap in stem cell funding could drive Australian brain drain p834 Elie Dolgin doi:10.1038/nm0810-834a Full Text | PDF Lab-grown organs seen as remedy for long donor waitlists p834 Roxanne Palmer doi:10.1038/nm0810-834b Full Text | PDF Stem cells serve as new platform for biodefense preparedness p835 Mike May doi:10.1038/nm0810-835 Full Text | PDF Educators dissect the future of medical training p836 Roxanne Palmer doi:10.1038/nm0810-836a Full Text | PDF Teaching hospitals urged to disclose clinical conflicts of interest p836 Roxanne Palmer doi:10.1038/nm0810-836b Full Text | PDF Big pharma moves from 'blockbusters' to 'niche busters' p837 Elie Dolgin doi:10.1038/nm0810-837a Full Text | PDF Advocates to bring rare disease philanthropy under one umbrella p837 Elie Dolgin doi:10.1038/nm0810-837b Full Text | PDF News in brief pp838 - 839 doi:10.1038/nm0810-838 Full Text | PDF Straight talk with ... Peter Piot p840 Asher Mullard doi:10.1038/nm0810-840 Peter Piot, formerly executive director of UNAIDS, will become director of the London School of Hygiene and Tropical Medicine next month. Speaking with Asher Mullard, he discusses the changing nature of global health research. Abstract | Full Text | PDF Parse the salt, please pp841 - 843 Stephen Strauss doi:10.1038/nm0810-841 Salt has been humanity's great taste enhancer, preservative and all-around go-to food ingredient for 8,000 years. But the ubiquitous white crystal is now thought to have caused an epidemic of heart attacks and strokes. In response, many food manufacturers are devising new ways to curb sodium intake while trying to maintain food's saline-stoked good flavor. Stephen Strauss gets a taste of the leading technological solutions for cutting back on the tabletop seasoning. Full Text | PDF Tech meets bio pp844 - 847 Monica Heger doi:10.1038/nm0810-844 IBM computers and Microsoft software have been mainstays of biomedical studies for years. But, in the past decade, software and technology companies have increasingly been taking a more active role in biological research. Monica Heger profiles four of the movers and shakers who have been leading the charge. Full Text | PDF Prepare for the long haul of drug monitoring p848 Richard Gliklich doi:10.1038/nm0810-848 As concerns have emerged in recent years over medications such as Vioxx and now Avandia, the need to improve the surveillance of approved drugs has become increasingly apparent. To ensure the success of the drugs they develop, biomedical researchers should track a wider set of clinical endpoints in drug trials and prepare to distinguish between real and false risks suggested by long-term safety monitoring. Full Text | PDF Book Review Top What's in a name? p849 David Rubinsztein reviews Disturbances of the Mind by Douwe Draaisma and Barbara Fasting doi:10.1038/nm0810-849 Full Text | PDF News and Views Top Neutrophils release brakes of coagulation pp851 - 852 Wolfram Ruf and Zaverio M Ruggeri doi:10.1038/nm0810-851 Blood coagulation protects from microbial infections. A recent study now shows that neutrophils fine tune the procoagulant response to invading pathogens (pages 887-896). Neutrophils degrade an inhibitor of coagulation, locally 'trapping' bacteria in small blood vessels. But they also increase blood clots in large vessels in the absence of infection, which may be relevant for the treatment of thrombosis. Full Text | PDF See also: Article by Massberg et al. Turning on the angiogenic microswitch pp853 - 854 Hanna M Eilken and Ralf H Adams doi:10.1038/nm0810-853 The angiogenic switch, which leads to the activation of endothelial cell proliferation and the growth of new blood vessels, is a crucial step in tumorigenesis. A study now shows that this process is linked to a microRNA in endothelial cells (909-914). Blocking microRNAs may offer new avenues for antiangiogenesis therapy to treat cancer. Full Text | PDF See also: Letter by Anand et al. A needle in the 'cancer vaccine' haystack pp854 - 856 Anne Gallois and Nina Bhardwaj doi:10.1038/nm0810-854 Vaccines can prevent infections by several pathogens. Success, however, has been limited for other chronic diseases, reflecting a constraint for effectively manipulating the human immune system. The results from four studies describe a novel dendritic cell (DC) subset in humans that may be crucial for the design of vaccines against cancer and other chronic diseases. Full Text | PDF Glutamate joins the ranks of immunomodulators pp856 - 858 Anna M Hansen and Rachel R Caspi doi:10.1038/nm0810-856 Elevated amounts of glutamate, which acts as a neurotransmitter but is also a neurotoxin, are a hallmark of the autoimmune neurological disease multiple sclerosis and may contribute to its pathology. The discovery that a receptor for glutamate can inhibit the development of autoimmunity and protect from neuroinflammation in a mouse model of multiple sclerosis suggests that glutamate may also have a protective role and that its receptor may represent a therapeutic target (pages 897-902). Full Text | PDF See also: Article by Fallarino et al. Targeting dendritic cell metabolism in cancer pp858 - 859 Laurence Zitvogel and Guido Kroemer doi:10.1038/nm0810-858 Cancers can compromise the capacity of the host immune system to recognize tumor antigens. Recent findings now show that increased accumulation of lipids in dendritic cells in tumors can impair presentation of tumor antigens[mdash]which is crucial for activation of the immune system[mdash]providing a conceptual framework that may help increase the efficacy of therapeutic vaccines (pages 880-886). Full Text | PDF See also: Article by Herber et al. Medicine JOBS of the week Saskatchewan Research Chair in Multiple Sclerosis Clinical Research Saskatchewan Health Research Foundation (SHRF) Saskatchewan, Canada Medical Scientific Expert - Neuroscience Fforde Management Switzerland Postdoctoral Fellow University of Illinios at Chicago Chicago, IL 60612 Pharmaceutical Primary Care Sales Rep Neuroscience Lilly USA, LLC Santa Barbara, CA More Science jobs from Medicine EVENT Frontiers in Cell Biology and Medicine 26.-29.09.10 York, UK More science events from Community Corner Top Mutant mice challenged as models of injury in the central nervous system p860 doi:10.1038/nm0810-860 Full Text | PDF Between Bedside and Bench Top A double agent in cancer  Macrophages engulf microbes and cellular debris to protect us from disease and help repair wounded tissues. In cancer, they also infiltrate the tumor, but studies in humans and mice now uncover more sinister roles for these immune cells in cancer. In 'Bedside to Bench', Christiana Ruhrberg and Michele De Palma scrutinize a clinical study where the presence of macrophages correlates with a high risk of disease progression in people with Hodgkin's lymphoma, indicating a clinical value of macrophages as biomarkers of survival. The authors also emphasize how characterizing of the mechanisms by which subpopulations of macrophages promote tumor cell motility and angiogenesis might help in the development of antiangiogenic therapies to stop tumor progression. In 'Bench to Bedside', Joseph Qualls and Peter Murray examine a study that shows how stopping migration of macrophages into the tumor can impair tumor regrowth after radiation treatment. A double agent in cancer: Deciphering macrophage roles in human tumors pp861 - 862 Christiana Ruhrberg and Michele De Palma doi:10.1038/nm0810-861 Full Text | PDF A double agent in cancer: Stopping macrophages wounds tumors pp863 - 864 Joseph E Qualls and Peter J Murray doi:10.1038/nm0810-863 Full Text | PDF Research Highlights Top Research Highlights pp866 - 867 doi:10.1038/nm0810-866 Full Text | PDF Brief Communication Top Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy pp869 - 871 Carlo Viscomi, Alberto B Burlina, Imad Dweikat, Mario Savoiardo, Costanza Lamperti, Tatjana Hildebrandt, Valeria Tiranti and Massimo Zeviani doi:10.1038/nm.2188 Ethylmalonic encephalopathy is a metabolic disease affecting many organ systems that is caused by the inability to metabolize sulfide. Now, Zeviani and colleagues have discovered a dual drug regimen that can ameliorate disease in affected children. First paragraph | Full Text | PDF Advertisement Type 2 Diabetes Nature Collection Produced with content from Nature Reviews Drug Discovery Read online for FREE Produced with support from   Articles Top CIB1 is a regulator of pathological cardiac hypertrophy pp872 - 879 Joerg Heineke, Mannix Auger-Messier, Robert N Correll, Jian Xu, Matthew J Benard, Weiping Yuan, Helmut Drexler, Leslie V Parise and Jeffery D Molkentin doi:10.1038/nm.2181 Increased levels of Ca2+ in cardiomyocytes promote cell growth that, under stressful conditions, such as those caused by hypertension, can contribute to heart remodeling and failure. Joerg Heineke et al. identify a new regulator of this type of maladaptive cardiac muscle growth in mice, the calcium-binding protein CIB1, which they show regulates the membrane-association of calcineurin and downstream signaling. Abstract | Full Text | PDF Lipid accumulation and dendritic cell dysfunction in cancer pp880 - 886 Donna L Herber, Wei Cao, Yulia Nefedova, Sergey V Novitskiy, Srinivas Nagaraj, Vladimir A Tyurin, Alex Corzo, Hyun-Il Cho, Esteban Celis, Brianna Lennox, Stella C Knight, Tapan Padhya, Thomas V McCaffrey, Judith C McCaffrey, Scott Antonia, Mayer Fishman, Robert L Ferris, Valerian E Kagan and Dmitry I Gabrilovich doi:10.1038/nm.2172 Dendritic cells in individuals with cancer and in mouse tumor models show an increase in triacylglycerides that seems to impair their antigen-processing capability and could thus contribute to tumor immune tolerance. This aberrant lipid load results from tumor-induced elevation of the scavenger receptor Msr1 on dendritic cells, and it can be targeted therapeutically to improve the efficiency of anticancer vaccines. Abstract | Full Text | PDF See also: News and Views by Zitvogel & Kroemer Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases pp887 - 896 Steffen Massberg, Lenka Grahl, Marie-Luise von Bruehl, Davit Manukyan, Susanne Pfeiler, Christian Goosmann, Volker Brinkmann, Michael Lorenz, Kiril Bidzhekov, Avinash B Khandagale, Ildiko Konrad, Elisabeth Kennerknecht, Katja Reges, Stefan Holdenrieder, Siegmund Braun, Christoph Reinhardt, Michael Spannagl, Klaus T Preissner and Bernd Engelmann doi:10.1038/nm.2184 Neutrophils release the serine proteases neutrophil elastase and cathepsin G, which have microbicidal activity and thereby contribute to the innate immune response. Steffen Massberg et al. now show that these neutrophil serine proteases, in association with extracellular nucleosomes, can also promote coagulation and thrombosis within large blood vessels. In a mouse model of systemic bacterial infection, these proteases spurred intravascular coagulation in the microcirculation of the liver, limiting bacterial tissue invasion. These findings point to a role for thrombosis in antimicrobial defense. Abstract | Full Text | PDF See also: News and Views by Ruf & Ruggeri Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation pp897 - 902 Francesca Fallarino, Claudia Volpi, Francesco Fazio, Serena Notartomaso, Carmine Vacca, Carla Busceti, Silvio Bicciato, Giuseppe Battaglia, Valeria Bruno, Paolo Puccetti, Maria C Fioretti, Ferdinando Nicoletti, Ursula Grohmann and Roberto Di Marco doi:10.1038/nm.2183 Excessive glutamate seen in multiple sclerosis leads to excitotoxicity and neuronal dysfunction. Fallarino et al. find that the clinical signs and neuroinflammation in experimental autoimmune encephalitis is worsened in mice deficient in the metabotropic glutamate receptor-4. Small molecules that enhance signaling through this receptor suppress neuroinflammation by promoting T regulatory cell development and suppressing TH17 responses. This cross-talk between the nervous and immune system suggests an endogenous mechanism to suppress neuroinflammation in the context of multiple sclerosis. Abstract | Full Text | PDF See also: News and Views by Hansen & Caspi Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia pp903 - 908 Michael G Kharas, Christopher J Lengner, Fatima Al-Shahrour, Lars Bullinger, Brian Ball, Samir Zaidi, Kelly Morgan, Winnie Tam, Mahnaz Paktinat, Rachel Okabe, Maricel Gozo, William Einhorn, Steven W Lane, Claudia Scholl, Stefan Frohling, Mark Fleming, Benjamin L Ebert, D Gary Gilliland, Rudolf Jaenisch and George Q Daley doi:10.1038/nm.2187 The authors uncover a new role for the RNA-binding protein Msi2 in the regulation of hematopoietic stem cell homeostasis and leukemogenesis. Msi2 is required for the maintenance of the balance between progenitor renewal and differentiation, and its overexpression cooperates with oncogenic events to induce aggressive leukemia. Msi2 expression is also elevated in human myeloid leukemias and may be a new prognostic marker and therapeutic target in acute myeloid leukemia. Abstract | Full Text | PDF Letter Top MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis pp909 - 914 Sudarshan Anand, Bharat K Majeti, Lisette M Acevedo, Eric A Murphy, Rajesh Mukthavaram, Lea Scheppke, Miller Huang, David J Shields, Jeffrey N Lindquist, Philip E Lapinski, Philip D King, Sara M Weis and David A Cheresh doi:10.1038/nm.2186 Sudarshan Anand et al. show that endothelial cell expression of the microRNA miR-132 targets a negative regulator of Ras pathway signaling and thereby releases a brake to new blood vessel formation. miR-132 expression is upregulated in the endothelium of human hemangioma and tumor samples, and an antagonist of miR-132, delivered specifically to tumor endothelium using an integrin-targeted nanoparticle, was able to inhibit tumor angiogenesis and growth in mice. First paragraph | Full Text | PDF See also: News and Views by Eilken & Adams Technical Reports Top Dissolving polymer microneedle patches for influenza vaccination pp915 - 920 Sean P Sullivan, Dimitrios G Koutsonanos, Maria del Pilar Martin, Jeong Woo Lee, Vladimir Zarnitsyn, Seong-O Choi, Niren Murthy, Richard W Compans, Ioanna Skountzou and Mark R Prausnitz doi:10.1038/nm.2182 Sullivan and his colleagues describe a novel microneedle patch-based system for vaccine delivery that targets the skin's antigen-presenting cells, providing improved immunogenicity and eliminating the hazards associated with using hypodermic needles. The group demonstrates the feasibility of this approach for influenza prophylaxis, whereby vaccine is encapsulated within microscopic polymeric needles that dissolve in the skin in minutes. Abstract | Full Text | PDF A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography pp921 - 926 Tarik F Massoud, Ramasamy Paulmurugan and Sanjiv S Gambhir doi:10.1038/nm.2185 Tarik Massoud and colleagues offer a new, noninvasive molecular imaging technique based on split reporter complementation for quantifying and imaging protein-protein interactions[mdash]cytoplasmic and nuclear[mdash]in vivo using positron emission tomography. They use a split reporter system based on the enzyme herpes simplex virus type 1 thymidine kinase, an approach designed to significantly improve the sensitivity and dynamic range of imaging protein-protein interactions. Abstract | Full Text | PDF Regeneration and orthotopic transplantation of a bioartificial lung pp927 - 933 Harald C Ott, Ben Clippinger, Claudius Conrad, Christian Schuetz, Irina Pomerantseva, Laertis Ikonomou, Darrell Kotton and Joseph P Vacanti doi:10.1038/nm.2193 Harald Ott and his colleagues build on their earlier work, based on reconstruction of a decellularized heart, to develop a new way to bioengineer a functioning lung. Through a process of decellularization, seeding with endothelial and epithelial cells, and maturation in an innovative bioreactor system, followed by transplantation into rats of the regenerated lungs in orthotopic position, the group was able to demonstrate adequate ventilation, blood flow and gas exchange in vivo for short periods of time. Abstract | Full Text | PDF Top Advertisement Register for a free print copy of Lab Offers and you could win a Dell Netbook Lab Offers provides researchers like you with exclusive discounts from the top suppliers of antibodies, reagents, cell/tissue cultures, imaging equipment, DNA sequencing, RNA isolation & purification, gene expression analysis, chromatography, lab consumables and so much more! Register at www.nature.com/laboffers before September 30 to receive a FREE print copy. One lucky registrant will win a Dell Netbook!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact nature...@nature.com More Nature Events

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